Bibliographic
The aim of this study was to explore whether sildenafil could reverse the memory impairments shown by SAMP8 mice as well as the underlying mechanisms.Sildenafil administration (7.5 mg/kg for 4 weeks) to 5-month-old SAMP8 mice attenuated spatial learning and memory impairments shown by these mice in the Morris Water Maze. Tau hyperphosphorylation (AT8 but not PHF-1 epitope) shown by SAMP8 mice at this age was also decreased in the hippocampus of sildenafil-treated mice, an effect probably related to a decrease in cyclin-dependent kinase 5 protein expression and activity (p25/p35 ratio). Sildenafil treatment was associated with phosphosphorylated Akt, which was associated with an increase of glycogen synthase kinase-3 phosphorylation, providing a plausible explanation for the reductions in tau hyperphosphorylation and attenuation of cognitive deficits shown by 9-month-old SAMP8 mice. Overall, sildenafil might be beneficial in age-related brain dysfunction and could be an emerging candidate for the treatment of other neurodegenerative diseases.